Small Increased Birth-Defect Risk Found With Methylphenidate for ADHD

Boston—Increasing use of attention-deficit hyperactivity disorder (ADHD) medications in adults is heightening concerns about what effect the drugs might have on fetuses in early pregnancy.

A report published in JAMA Psychiatry points to a dearth of evidence on whether exposure to the medications can increase birth defects.

To remedy that, researchers from Brigham and Women’s Hospital (BWH) collaborated with investigators in five Nordic countries to obtain data from multiple large cohorts to look at possible increased risk from the most commonly used ADHD medications. Results indicate that, while methylphenidate was associated with a small increased risk of heart defects, amphetamines were not.

The results included 1.8 million pregnancies from the U.S. Medicaid Analytic eXtract (2000-2013), with replication of initial safety indicators in 2.5 million pregnancies in the Nordic Health registries (2003-2013). Study authors note a potential small increased risk of cardiac malformations associated with methylphenidate use (pooled relative risk, 1.28; 95% CI, 1.00-1.64), adding that neither methylphenidate nor amphetamines were associated with an increased risk for malformations overall, however.

“Our findings suggest a small increase in the risk of cardiac malformations associated with first-trimester exposure to methylphenidate, but not to amphetamines,” explained corresponding author Krista Huybrechts, PhD, of the BWH Division of Pharmacoepidemiology and Pharmacoeconomics. “This information may be important to patients and their physicians as they weigh the risks and benefits of alternative treatment strategies for attention deficit hyperactivity disorder.”

Based on both populations, researchers determined a 28% increased risk of heart malformations after first-trimester exposure to methylphenidate, which translates to three additional infants born with congenital heart defects for every 1,000 women treated with methylphenidate during the first trimester of pregnancy.

“Our study markedly expands the evidence base regarding the safety of methylphenidate use in pregnancy,” Huybrechts pointed out. “Although the absolute risk is small, it is nevertheless important evidence to consider when treating young women of reproductive age and pregnant women.”